Melatonin (N-acetyl-5-methoxytryptamine), which is a hormone synthesized and secreted principally in the pineal gland, increases in dark environments and decreases in light environments. Melatonin acts suppressively on pigment cells and the female gonads, and acts as a synchronous factor of biological clock while taking part in transmittance of photoperiodic code. Therefore, melatonin is expected to be usable for the treatment of diseases related to melatonin activity, such as reproductive and endocrinic disorders, sleep-awake rhythm disorders, jet-lag syndrome, various disorders related to aging and the like. It has been clarified that the production amount of melatonin decreases with aging and there is a report documenting that retention of the production amount of melatonin could prevent aging itself [Ann. N.Y. Acad. Sci., Vol. 719, pp. 456-460, (1994)]. However, since melatonin is easily metabolized by metabolic enzymes in vivo [Clinical Examinations, Vol. 38, No. 11, pp. 282-284 (1994)]. Therefore, melatonin is not entirely suitable as a drug.
US2003/0216456 discloses a compound represented by the formula:
wherein A is C1-4 alkylene or 1,2 disubstituted cyclopropyl; B is C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkoxy, or C1-4 alkylamino; X is hydrogen, halogen, C2-4 alkenyl, C1-6 alkyl, furyl, or phenyl optionally substituted with halogen, C1-6 alkoxy or haloalkyl; and Y is hydrogen, phenyl, or C1-6 alkyl optionally substituted with phenyl, which has an affinity for melatonin receptor and is useful as a therapeutic agent for circadian rhythm-related disorders. Moreover, a compound similar to the above-mentioned compound is also disclosed in Bioorg. Med. Chem. Lett. Vol. 14, pp. 1197-1200 (2004) and Bioorg. Med. Chem. Lett. Vol. 14, pp. 3799-3802 (2004).
U.S. Pat. No. 6,569,894 discloses a compound of the formula:
wherein the dashed line represents a single or double bond; R1 and R2 are each independently hydrogen or halogen; R3 is hydrogen or C1-4 alkyl; R4 is C1-4 alkyl, C3-6 cycloalkyl, C1-3 haloalkyl, C2-6 alkenyl, C1-4 alkoxy, C1-2 trifluoromethylalkyl or C1-4 alkylamino; R5 is hydrogen, halogen, C1-4 alkyl or C1-4 alkoxy; Y is hydrogen or halogen; W is ethylene or 1,2 disubstituted cyclopropyl group; m is 1 or 2; and n is 1 to 9, which has an affinity for melatonin receptor and is useful as a therapeutic agent for circadian rhythm-related disorders.
U.S. Pat. No. 6,034,239 discloses a compound represented by the formula:
wherein R1 represents an optionally substituted hydrocarbon group, an optionally substituted amino group or an optionally substituted heterocyclic group; R2 represents a hydrogen atom or an optionally substituted hydrocarbon group; R3 represents a hydrogen atom, an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; X represents CHR4, NR4, O or S wherein R4 represents a hydrogen atom or an optionally substituted hydrocarbon group; Y represents C, CH or N, provided that when X is CH2, Y is C or CH;  represents a single bond or a double bond; ring A represents an optionally substituted 5- to 7-membered oxygen-containing heterocyclic ring; ring B represents an optionally substituted benzene ring; and m represents an integer of 1 to 4, or a salt thereof, which has an affinity for melatonin receptor and is useful as a therapeutic agent for sleep disorder.